Damage accumulation in tendons and tendon tears are a major source of musculoskeletal disability, afflicting the entire spectrum of society. Despite the importance of these problems, clinicians have little scientific basis for treatment recommendations because mechanisms whereby exercise may improve tendon homeostasis and resistance to injury, mechanisms responsible for the poor healing of fatigue damaged tendons, and the effect of activity on the healing of repaired diseased tendons are unknown. Previous studies have investigated the effects of exercise and laceration, but only in healthy tendon. We have developed and extensively characterized an in vivo model of fatigue damage accumulation in the rat patellar tendon, and now propose to study the response of fatigue damaged tendon to exercise and/or laceration. These studies, using this clinically relevant model of diseased tendons, will provide the foundation for novel and improved treatment strategies. PUBLIC HEALTH RELEVANCE: The major goal of this project is to explore the effect of tendon overuse damage on the response of tenocytes to exercise and laceration. Successful completion of the proposed studies will provide the foundation for novel and improved treatment strategies for tendon injury.